P,P{40 -Disubstituted alpha-trichloromethylbenzyl ethers

ABSTRACT

P,P&#39;&#39;-Disubstituted Alpha -trichloromethylbenzylphenyl ethers are a new class of compounds which show varying degrees of utility as selective or nonselective biodegradable insecticides and/or larvicides.

United States Patent Metcalf et al.

July 8, 1975 P,P -DISUBSTITUTED ALPHA-TRICHLOROMETHYLBENZYL ETHERS Inventors: Robert L. Metcalf; Inder Kapoor;

Asha Hirwe, all of Urbana, lll.

Assignee: University of Illinois Foundation,

Urbana, 111.

Filed: Dec. 26, 1972 Appl. No: 318,206

US. Cl 260/613 R; 260/612 R; 424/341 Int. Cl. .1 C07c 43/20 Field of Search 260/613 R, 612 R References Cited UNITED STATES PATENTS 8/1952 Ladd et al 260/612 R OTHER PUBLICATIONS Hirwe et al., J AGR, Food Chem 20, 818 (1972).

Primary Examiner-Bernard Helfin Assistant Examiner-Nicky Chan Attorney, Agent, or Firm-Merriam, Marshall, Shapiro & Klose 4 Claims, No Drawings P,P'-I)ISUBSTITUTED ALPHA-TRICHLOROMETHYLBENZYL ETHERS SUMMARY OF THE INVENTION BACKGROUND oF THE INVENTION The p,p-disubstituted a-trichloromethylbenzylphenyl ethers'of the present invention are a novel class of compounds. Their properties are such that they exhibit utilities as selective or nonselective insecticides and/or larvicides. In addition, many of the members of the class of compounds of the present invention also exhibit properties of biodegradability. In view of the fact that DDT [1, l, I trichloro-2,2-bis( pchlorophenyl)ethane], the insecticide in most widespread use today, is not biodegradable, these properties take on added importance by serving to minimize one of the greatest deficiencies of prior art insecticides.

There is growing concern about the continuing liberation of vast quantities of DDT into the environment. The very qualities which make DDT such an effective contact or residual insecticide, i.e., its very low water solubility and high lipid solubility, caused by the nonpolarity of the DDT molecule, result in its accumulation in the fatty or lipid tissues of animals. These properties result in ever increasing concentrations in the tissues of carnivorous animals at the upper ends of food chains. The problems associated with this magnification phenomenon are further intensified by the enzy-- matic metabolic conversion of DDT to the even more stable dehydrochlorination product, DDE l ,ldichloro-2,2-bis(p-clorophenyl)ethylene].

Drug metabolizing enzymes, known as multifunction oxidases (MFO), which play a dominant role in detoxifying insecticides in both insects and higher animals,

such as birds, fish, and mammals do not function on DDT and its metabolic derivatives DDE and DDD (or TDE) l,1-dichloro-2,2-bis(p-chlorophenyl')ethane]- as substrates. This single factor accounts for their storage and accumulation in animal tissues, especially at the higher ends of food chains.

Certain known symmetrical DDT analogs, suchas methoxychlor [1,1 ,l-trichloro-,2,2-bis(pmethoxyphenyhethane] and methiochlor [1,1,1- trichloro-2,2-bis-(p-methiophenyl)ethane] are readily attacked by MFO enzymes, which metabolically convert or biodegrade such analogs into environmentally acceptable products which are rapidly eliminated by animals. Thus, methoxychlor is an example of a biodegradable insecticide which is not generally accumulated in animal tissues and is, thus, a more prudent choice than DDT for a variety of uses where environ-' mental pollution is an important factor. However, me- I I thoxychlor andother known symmetrical DDT analogs (e.g., methylchlor [1,1 ,1-trichloro-2,2-bis(pmethylphenylJethane] and methiochlor), while exhibit- I ing satisfactory.insecticidal activity towards certain species of insects, exhibit considerably less insecticidal activity than DDT towards other species of insects.

One attempt to remedy the problems of the prior art is disclosed in the copending application of Metcalf et al., Insecticidal Biodegradable Analogues of DDT", Ser. No. 147,241, filed May 26, 1971, and having a common assignee with the present application. These asymmetrical analogues of DDT have in general proved to be biodegradable and effective as insecticides. The compounds in accordance with the present invention, however, offer a mechanism of molecular cleavage of the -O--CH(CCl )bonds, whereby biodegradability. may be increased. In addition to biodegradability, certain of the compounds of the present invention offer outstanding toxicity as either selective or non-selective insecticides. The compounds of th'epresent invention are further distinguished from prior art insecticides in that they breakdown upon prolonged exposure to sunlight, which would prove to be beneficial in applications where persistence of the insecticide is either not necessary or undesirable.

DESCRIPTION OF THE INVENTION It has been found from metabolic studies on insects. and mice, using a model ecosystem and the methods described in Kapoor, et al., 18(6) J.Agr., Food Chem. 1 I45 (I970), Metcalf, et al., J. Environ. Sci. Technol. 709 (1971) and also in the copending application of Metcalf et al., Insecticidal Biodegradable Analogues of DDT", Ser. No. 147,241, filed May 26, l97l, and having a common assignee with the present application, that certain p.p-disubstituted a-trichloromethylbenzylphenyl ethers with various substituent groups are readily attacked by multifunction oxidase (MFO) enzymes, and thus are substantially biodegradable. Insecticidal activity studies involving both DDT resistant and regular strains of house flies. the blow fly. various types of mosquitoes and other insects have further indicated that the compounds of the present invention are effective insecticides.

The compounds of the present invention are p,p'- disubst ituted a-trichloromethylbenzylphenyl ethers. Preferably, the two p,p substituent groups are chosen from the group consisting of Cl, CH CI-I,,O, and C H5O. These compounds are biodegraded and metabolically converted to environmentally acceptable products by attack by MFO enzymes on the various substituents of the aryl rings to produce waterpartitioning moieties. Also, further biodegradability is provided by separation of the two aryl rings by cleavage of the -OCH(CCl )-bond, which is not present in DDT or its symmetrical or asymmetrical analogues. The presence of an oxygen atom between the two aryl rings of the compounds of the invention provides a means of increasing biodegradability and does not destroy toxicity to insects.

Such p,p'-disubstituted a-trichloromethylbenzylphenyl ethers may be synthesized by condensing the appropriate a-trichloromethylbenzyl alcohol (DDT-type carbinol) with equimolar quantities of the appropriate phenol using concentrated sulfuricacid or polyphosphoric acid as the condensing agent.

EXAMPLE-l moved under vacuum and the residue was recrystallized from ethanol to give a-trichloromethyl-pchlorobenzyl p-chlorophenyl ether, mp 101C. This method of synthesis is referred to in Table 1 as method A.

EXAMPLE ll Employing similar techniques, other compounds of the present invention were prepared. The properties and structures are set forth in Table l.

The compounds of the present invention were tested for insecticidal activity by standard methods, and compared with the insecticidal activities of DDT and symmetrical analogs of DDT, such as methoxychlor. Toxicological methods for the determination of the topical LD values to adult female SNAmM and R houseflies,

Musca domestica L. and to Phormia regina, and LC values to C'Iex pipiens quinquefasciatus Say, and Anopheles albimanus Weid mosquitoes were described by Metcalf et al.. 44 Bull. World Health Org; 363 1971 The methods for evaluation of metabolism by mouse liver homogenate and by female Rsp housefly and saltv marsh caterpillar larvae Estigmene acrea Drury, were describedby Metc alf et al., 5. .1. Environ. Sci. Tech. 709

(1971). The results are detailed in Table 11.

TABLE I CCl3 Chemical Structures and Properties of a-Trich1oromethylbenzylphenyl Ethers Method of R R mp "C synthesis nmr data. a fippm C1 C1 101 A a-H 5.4(s)

CH;,O Ch O 90 B a-H 5.36 (s). OCH 3.36

CH CH Liquid B 01-11 5.41 (s). CH 2.33 (s),

v 7 CH 2 83 (s) C H,,O C. .H .,O Liquid B u-H 5.21 (s). OCH 3.61-

4.13 (m). CH;,1.2-1.5 (m) c1 c11 0 90 B a-H 5.43 (50, ocl-r, 3.43 (s) (1 C H O Liquid 1 A 01-11 5.43 (s), OCH 3.83-

4.2(g). CH;,1.26-1.5(t)

(H O C H O B ,a-H 5.43 (s), OCH, 3.85-

4.2 (q). CH 1.3-l.5(t), OCH 3.73(s) (H 11 0 Liquid B a-H 532(5), CH;, 2.16(s),

OCH 3.75-4.1(q) CH cH, cmo 142 B a-H 5.62.01 2.33m.

OCH 3.83(s) TABLE ll Toxicity of u-Trichloromethylhenzylphenyl Ethers to Insects Topical LD [Lg per g for Musca dunwxliza LC ppm Cu [ex Anopheles Substrtuents SNAlDM Rsl' 1 Phurmiu reginu faliguns albimanus 1 R R Alone pb SR Alone 1 pb SR Alone pb SR larvae larvae 1 C1 C1 90 1.0 500 180 i 3.6 250 250 0.035 0.014 11 (H O CH;;() 300 14.0 22 500 57.5 8.7 1'25 82.5 1.5 0.51 0.10 111 CH CH 265 90 2.9 500 145 3 135 1.35 0.12 018 IV C ll-,0 H -,O 27.0 13.0 2.1 42 24.5 1.7 16.5 16.5 1.0 0.11 0.07 V C1 CH O 107.5 17.0 6.3 82.5 1.6 205 115 1.8 0.14 0.038 V1 C1 H O 18.5 9.5 1.9 31 12. 2.5 31.2 31.2 1.0 0.067 0044 V11 CH O 'C- .H -,O 45.0 5.0 9.0 90 14.0 6.4 30.0 16.0 1.9 0.14 0.034 V111 CH; C H -,O 72.5 20.5 3.5 65 22.0 2.9 46.2 30.0 1.5 0.18 0.066 1X CH CH O 500 39.0 13 500 4 250 250 0.65 1.0

houseflies (22 Compounds of the Present Invention are Effective Insecticides 1 The data of Table II indicate the insect toxicity of 9 different a-trichloromethylbenzylphenyl ethers gina, and to Culex fatigans and Anopheles albimdnux.

The compounds with the highest intrinsic toxicity were,

Musca domestica (S M and R strains), Phormia re- OC I-IQ (IV) and CH O, CH O (II), havingsynergized ILD50 values of 5.0 9.5, 13.0, and M respectively. Compounds IV and VII were quite toxic to Phorrnia,

which is deficient in MP0, with synergized LD values ci o, oc u (VII), c1, oc u (v1), and c nsogf, OC2H5 (IV). The CH3O,.OCH3 compound (II) had the 7 largest SR value in both susceptible and resistant 8.7), indicating rapid detoxication. while the Cl, OC H compound (VI) had the lowest SR values (l.92.5).

v The most effective insecticide generally was VI (oz-trichloromethyl-p-ethoxybenzyl p-chlorophenyl ether) which had the lowest LD values to the housefly and was only slightly less toxic to'Phormia than the p',p'- diethoxy compound IV and to mosquito larvae than compound I. Toxicity in the symmetrical substituents was in the general order of C H O Cl CH O CH .The synergistic ratios or SR values (LD alone/LD synergized with piperonyl butoxide) shown in Table II indicate the role of the multifunction oxidase (MFO) 0.014 for- C'ulex of 16.5- and l6.0'respecti'vely As a larvicide CLCI (I) was the most] toxic, with an LC ppm of 0.035 and spectively.

: Employing the tech niq ues'disclosed i'n Metcalf etaL,

5 J. Environ. Sci. Technol. 709( 1971,), the compounds h of the present invention have been shownto be biode *gradable. i 1- j The foregoing detailed description has been givenfor.

clearness of understanding only, and no unnecessary limitations should be understood therefrom as modifications will be obvious to those skilled in. the art.

What is claimed is: l. Insecticides having the formula where R, and R are the same or different C, to C iallts oxy groups. 1

2. An insecticide as defined in claim 1 wherein R, and R are each C H O.

3. An insecticide as defined in claim I wherein R and R are each C H O.

4. An insecticide as claimed in claim 1 wherein R is.

CH O and R is CgH50.

fatigqns and Anopheles albiman'us, vre-.

UNITED STATES PATENT AND TRADEMARK OFFICE CERTIFICATE OF CORRECTIN PATENT NO. ,394,092 DATED 1 July 8, 1975 INVENTOMS) I Robert L. Metcalf, Inder Kapoor, Asha Hirwe It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Title, add "phenyl" to end of trichloromethylbenzyl- Column 1, line 2, add "phenyl" to end of trichloromethylbenzyl-. f

Column 4, fine 11, change "Clex" to Culex.

Table I, under nmr data, 5th item, change "5.43 (s to Table I, under nmr data, 6th item, change "4.2 (g) to Column 5, line 11, change (22 8.7) to (22 8.7)

Signed and 'geal ed this Tenth Day of August 1976 [SEAL] A I test:

Rum c. MASON c. MARSHALL DANN Arresting Officer Commissioner oflarenrs and Trademark: 

1. INSECTICIDES HAVING THE FORMULA
 2. An insecticide as defined in claim 1 wherein R1 and R2 are each C2H5O.
 3. An insecticide as defined in claim 1 wherein R1 and R2 are each CH3O.
 4. An insecticide as claimed in claim 1 wherein R1 is CH3O and R2 is C2H5O. 